Characterization and Longitudinal Monitoring of Muscular Phenotype in Patients Admitted to Intensive Care for Sepsis

Summary

Approximately 40% of patients develop muscle dysfunction during their stay in intensive care, particularly in the context of sepsis. This dysfunction represents an acquired muscle injury that is secondary to the primary illness that led to ICU admission. It affects both the limb muscles and the respiratory muscles of the thoracic cage. Clinically, this manifests as bilateral and symmetrical muscle weakness in the limbs, and contributes significantly to difficulties in weaning patients off mechanical ventilation.

The loss of muscle mass is directly correlated with the severity of the patient's clinical condition and can reach up to 20% of initial muscle mass within just ten days. This rapid and profound atrophy primarily results from an imbalance between increased muscle protein breakdown (catabolism) and insufficient protein synthesis (anabolism). The consequences of this muscle dysfunction are significant and far-reaching, with a marked negative impact on the overall prognosis.

This condition is associated with longer durations of mechanical ventilation and extended stays in the intensive care unit. Beyond the acute phase, patients often experience persistent reductions in physical performance, leading to long-term functional limitations that impair quality of life. Furthermore, ICU-acquired muscle dysfunction has been linked to increased long-term mortality, with excess deaths reported at both one year and five years following ICU discharge. This risk is especially pronounced when the muscle dysfunction is severe and continues beyond the hospitalization period.

Several risk factors for ICU-acquired muscle dysfunction may be modifiable, opening up the possibility for preventive or therapeutic interventions. Two main factors have been identified as particularly relevant: (1) the duration of immobility and muscular inactivity, and (2) the adequacy of nutritional support, especially regarding amino acid intake, which is critical for maintaining muscle protein synthesis.

In response to these factors, early and active mobilization of ICU patients has become a key component of recommended care, often in conjunction with strategies aimed at minimizing the use of sedative medications. These practices are encouraged by international guidelines, reflecting a growing consensus around the importance of maintaining some level of muscular activity even in critically ill patients. However, despite these recommendations, no definitive evidence has demonstrated a clear improvement in patient outcomes associated with early mobilization.

This lack of clear benefit may stem from multiple factors, including the variability in patient severity across clinical trials and, importantly, the timing of the intervention. The anabolic signals triggered by muscle contraction are only effective if they are strong enough to counterbalance the catabolic signals driven by inflammation, infection, or muscle hypoxia-all of which fluctuate over the course of illness and recovery.

Regarding nutritional interventions, the appropriate timing and quantity of calorie and protein intake necessary to support adequate anabolism and mitigate muscle loss remain controversial. Although amino acids are essential for muscle protein synthesis, current studies have not shown consistent improvements in muscle function based on different nutritional strategies in the ICU setting.

Given the high prevalence of ICU-acquired muscle dysfunction in patients with sepsis, its significant impact on outcomes, and the lack of an effective, evidence-based treatment, there is a pressing need to deepen our scientific understanding of this phenomenon. Improving knowledge in this area could lead to more targeted and effective interventions, ultimately helping to preserve muscle mass and function in critically ill patients and improving both their short- and long-term prognosis.

Conditions

• Sepsis
• Myopathy Critical Illness

Interventions

DIAGNOSTIC_TEST

Medical Research Council sum score (MRC-SS) test

Medical Research Council (MRC)-sumscore evaluates global muscle strength. Manual strength of six muscle groups (shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion) is evaluated on both sides using MRC scale

DIAGNOSTIC_TEST

Handgrip test combined with surface electromyography (sEMG)

Handgrip test combined with surface electromyography (sEMG) of the flexor digitorum superficialis

DIAGNOSTIC_TEST

Electrical activity during maximal voluntary contraction of the rectus femoris

Surface EMG amplitude (RMS) during maximal voluntary contraction measured by surface electromyography (sEMG) of the rectus femoris

DEVICE

Musculoskeletal Ultrasound

Measurement of the cross-sectional area (CSA) of the rectus femoris by ultrasound

DEVICE

Diaphragmatic ultrasound

Diaphragmatic ultrasound is a non-invasive technique that allows for sequential assessment of diaphragm mobility (excursion) and contraction (thickening) in mechanically ventilated patients

BIOLOGICAL

blood sampling

Blood samples are collected from a radial or femoral arterial catheter, which is part of the routine care of the patients. These samples are taken with the aim to: 1) describe the inflammatory profile (plasma measurements of CRP, IL-1, IL-6, TNFα, IL-10, fibrinogen, ferritin, cortisol), 2) assess organ dysfunction and calculate the SOFA score (arterial blood gases, lactate levels, liver function tests, complete blood count, and blood electrolyte panel)

DEVICE

Electroneuromyogram

Analysis of peripheral neurogenic and myogenic components involved in intensive care unit-acquired muscle dysfunction through the performance of an electroneuromyogram

DIAGNOSTIC_TEST

6-minute walk test

The 6-minute walk test (6MWT) is a simple test that requires a quiet, indoor, flat 30-meter course, ideally in a straight rectangular hallway

DIAGNOSTIC_TEST

Montreal Cognitive Assessment (MoCA)

The Montreal Cognitive Assessment (MoCA) is the most sensitive rapid assessment test and assesses cognitive functions most broadly (attention, concentration, executive functions, memory, language, visual-constructive abilities, abstraction, calculation, orientation).

BEHAVIORAL

MNA-SF

The MNA-SF (Short Form) is a simplified version that allows us to determine whether the elderly person is well nourished, at risk of malnutrition or malnourished.

Sponsors & Collaborators

• Centre Hospitalier de Saint-Brieuc

  lead OTHER

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-03-25

Primary Completion

2027-06-25

Completion

2027-06-25

Countries

• France

Study Locations